This project, currently with six principal investigators, is designed to characterize opioid compounds across the spectrum of their pharmacological activity. Initial evaluation is made of effects in displacing labeled opioids from brain membranes and determining receptor selectivity in this regard. Further in vitro evaluation is made of selective agonist and antagonist effects using smooth muscle and brain slice preparations. Behavioral evaluation is made of the discriminative stimulus, reinforcing stimulus, analgesia, respiratory, and dependence properties of the tested compounds. In addition to a full characterization of novel compounds, this group will engage in basic research with the more interesting of these and other opioids that warrant more extensive evaluation. Four of the six projects are concerned with identification and characterization of the in vitro and in vivo actions of opioids that interact at delta receptors. Three of the six projects involve an evaluation of the effect of tolerance at the level of analysis appropriate to that investigator. The effect of chronic opioid administration on adenylate cyclase and opioid-sensitive GTPase, on the reinforcing effects of opioids, and on analgesia and respiratory depression produced by opioids will be examined. The issue of comparing opioid efficacy among drugs will be evaluated in several of the projects. One project is devoted to synthesizing delta agonists and rare and useful opioids that will be of great help as tools to further our ability to describe opioid effects.